1, lamivudine resistance-related variants: reverse transcriptase gene variants can selectively appear during LAM treatment, including rtM204I/V/S in the C region with or without rtLl80M and rtVl73L in the B region. in vitro experiments have confirmed that LAM resistance variants can reduce the susceptibility of the virus to them by at least 100-fold, or even greater than 1000-fold. 2. Variants associated with adefovir resistance: ADV resistance is associated with rtA181T/V in the B region of reverse transcriptase and rtN236T variants in the D region. Some studies have shown that rtV214A or rtQ215S located in the C and D question regions and the combined variants of the two points may also be associated with ADV resistance. rtV variants in the polymerase gene region of HBV can increase the EC dose of the drug by 3-8 times and can lead to cross-resistance between ADV and TFV. The rtN236T variant that causes ADV resistance does not affect the susceptibility of the virus to LAM, but the rtA181T/V, rtV214A, and rtQ215S variants can lead to cross-resistance with LAM at the same time. 3, variants associated with entecavir resistance: the current findings show that a prerequisite for the development of ETV resistance is the presence of LAM resistant variants (rtM204I/V/S 4-rtLl80M). the presence of LAM resistant variants Itll69T, rtTl84A/G/I/S, rts202G/I or aM250V variants can cause cross-resistance to ETV resistance. In vitro tests showed that rtM250V increased the EC dose of the drug 9-fold in the absence of LAM resistance, while rtTl84G+rtS202I was not resistant. 4. Variants associated with telbivudine resistance: In vitro tests have shown that LAM-resistant HBV strains with rtM204I mutations or rtLl80M+rtM204V double mutations can reduce the LdT antiviral response rate by more than 1000-fold. In vitro trials also showed that LdT remained effective against HBV strains with rtM204V mutations (1.2-fold reduction in effect).